Genomic Characteristics and Risk Factor Analysis of Carbapenem-non-susceptible pseudomonas aeruginosa Causing Bacteremia in a Tertiary Hospital (2014-2023)

Background: Carbapenem-non-susceptible Pseudomonas aeruginosa (CnSPA) bloodstream infections (BSIs) are associated with high mortality and present significant clinical and public health challenges. This study aimed to investigate the genomic characteristics, resistance mechanisms, clinical features, and risk factors associated with CnSPA BSIs. Methods: A total of 52 consecutive, non-duplicate CnSPA isolates causing BSIs were collected from 2014 to 2023. Whole genome sequencing (WGS) was conducted to analyze antimicrobial resistance genes, sequence types (STs), serotypes, and mutations in carbapenem resistance-associated genes ( oprD , ampC , pbpA , pbpC ). Clinical data were collected to identify patient demographics, comorbidities, invasive procedures, and outcomes. Statistical analyses included logistic regression for risk factor identification and survival analysis for prognostic factors. Results: Among the 30 kinds of ARGs found, three carbapenemase encoding genes including bla KPC-2 (n = 1), bla VIM-2 (n = 1) and bla Pom-1 (n = 1) were identified. Genomic analysis revealed 36 distinct STs, with ST235, ST244, ST274, and ST357 being the most prevalent. Insertion sequences (ISs) were co-located with resistance genes in 96.2% of isolates, indicating a high potential for horizontal gene transfer. The serotypes analysis revealed a diverse distribution of O-antigen serotypes, with O11 (n = 15) being the most prevalent. oprD gene mutations were found in 92.3% of isolates. Mutations in ampC (88.5%) and pbpC (82.7%) contributed to resistance, but no pbpA mutations were detected. Clinically, the median patient age was 67 years, with male predominance (69.2%) and high mortality (38.5%). Logistic regression identified prolonged mechanical ventilation (≥ 7 days), History of carbapenem antibiotic exposure (≤ 90 days) and organ failure as independent risk factors for mortality, while prolonged indwelling catheterization (≥ 7 days) was an independent risk factor for polymicrobial infections. Conclusions: Our study showed that carbapenem resistance in CnSPA is predominantly driven by oprD inactivation and other gene mutations rather than carbapenemase production. The high genetic diversity among isolates emphasizes the need for robust genomic surveillance. Clinically, prolonged invasive procedures and critical illness contribute to adverse outcomes, underscoring the importance of infection control measures and timely management. These findings provide valuable insights into guiding antimicrobial stewardship and improving clinical outcomes for CnSPA BSI patients.